OHSU

Prostate Cancer Prevention Studies

Catechins and Omega-3 Fatty Acids Impact on Fatty Acid
Synthase in the Prostate: A Randomized Controlled Trial

Clinical trial studying the effects of fish oil and green tea in prostate cancer prevention


Background: Fatty acid synthase (FAS) is a lipogenic multienzyme that catalyzes the final step in de novo fatty acid synthesis. FAS more recently has been characterized as an oncogene [1] and is reported to be overexpressed in several tumor types including prostate. While FAS expression in cancer cells does not appear to be normally regulated by nutritional controls, Menendez et al demonstrated that addition of omega-3 fatty acids (ω-3 FA), docosahexanoic acid (DHA), alpha-linolenic acid, and ω-6 FA, ϒ-linolenic acid, resulted in significant inhibition of FAS expression and fatty acid production in FAS expressing SK-Br3 human breast cancer cells [2, 3]. Once transcribed, FAS activity is dependent upon the appropriate function of each of its component enzymes. Epigallocatechin-3-gallate (EGCG), a bioactive compound found in green tea, has been demonstrated to inhibit activity of transcribed FAS in prostate cancer cell lines [4].

The primary objective of our clinical trial is to elucidate, in men at high risk for prostate cancer, a potential biologic mechanism whereby EGCG, alone or in combination with ω-3 FA, may alter cellular composition and growth, thereby reducing overall risk of prostate cancer.

Methods: In this randomized, placebo-controlled intervention study, subjects are men with an initial negative biopsy considered to be at elevated risk of prostate cancer and scheduled for a repeat biopsy. The primary endpoints of this trial are FAS protein and mRNA expression, as measured by immunohistochemistry (IHC) and real-time (RT)-PCR, FAS activity and cell proliferation (Ki-67 expression) in benign, pre-neoplastic and neoplastic prostate tissue. Plasma EGCG and red cell fatty acid concentrations are also measured.

Subjects are randomized to receive green tea, fish oil, green tea+fish oil or double placebo for 12 weeks. Green tea supplements consist of extracted green tea polyphenols (75%) and no less than 30% EGCG (approximately 300mg) per 1000mg capsule. Fish oil capsules (1000mg) consist of ethyl esters of eicosapentaenoic acid (20:5n-3) and DHA (22:6 n-3). Men take 2 green tea and 3 fish oil capsules daily for a dose of 1.9g of EPA + DHA and 600 mg EGCG. To date, 72 men have completed the trial and 4 are currently enrolled. Our anticipated sample size is 120 men or 30 men per arm.

1. Migita T, Ruiz S, Fornari A, Fiorentino M, Priolo C, Zadra G, Inazuka F, Grisanzio C, Palescandolo E, Shin E, Fiore C, Xie W, Kung AL, Febbo PG, Subramanian A, Mucci L, Ma J, Signoretti S, Stampfer M, Hahn WC, Finn S, and Loda M. J Natl Cancer Inst 2009;101(7):519-532.
2. Menendez JA, Ropero S, Mehmi I, Atlas E, Colomer R, and Lupu R. Int J Oncol 2004;24(6):1369-1383.
3. Menendez JA, Colomer R, and Lupu R. Med Hypotheses 2005;64(2):342-349.
4. Brusselmans K, De Schrijver E, Heyns W, Verhoeven G, and Swinnen JV. Int J Cancer 2003;106(6):856-862.

Study Coordinator: Paige Farris
(503) 220-8262 x54868 email: farrisp@ohsu.edu

Genetic Susceptibility, Environment & Prostate Cancer Risk

A research study about genetics, diet and familial risk of prostate and reproductive cancers

The purpose of this study is to 1) learn about genes that may be linked to a higher risk of prostate cancer and 2) determine whether specific environmental and dietary factors combined with genetic factors protect or play a role in the risk of developing prostate or reproductive cancers.

This study is open to 1) Men identified as being high-risk for prostate cancer (i.e. referred for a prostate biopsy); 2) Men who previously participating in our Diet and Prostate Cancer Risk study; and 3) First degree relatives of participants in the first two groups (offspring, parents & siblings—both male & female)

Participants in the first two groups are the study probands. Probands are asked to complete a Family History of Cancer questionnaire and a Diet History Questionnaire. They also give blood & saliva samples. They then are asked to invite eligible family members to complete the same questionnaire online via a secure website.

Currently, we have enrolled over 300 subjects into this study with a goal of 1250 total participants (including family members)

Study Coordinators: Amy Palma & Paige Farris (503) 220-8262 x57280 / x54868
palmaa@ohsu.edu / farrisp@ohsu.edu

Diet and Prostate Cancer Risk Study

A case-control study to evaluate the association between dietary polyunsaturated fatty acid (omega 6 and omega 3) intake and prostate cancer risk

Recruitment for this study took place between 2001 and 2006. Approximately 730 subjects from the Portland VA Medical Center were enrolled. Analyses are still in progress, however, some findings have been published:

1. Statins and Prostate Cancer Risk: A Case-Control Study: The results of this case-control study suggest that statins may reduce the risk of total prostate cancer and, specifically, more aggressive prostate cancer. These findings were published in the American Journal of Epidemiology, 2005
2. Folate, Alcohol and Prostate Cancer Risk: Overall our analyses support a strong inverse association between dietary folate intake and prostate cancer risk (p =0.03, 95% CI), and this association appears to be modified somewhat by level of alcohol consumption (p =0.04, 95% CI). These findings were published in Nutrition and Cancer: An International Journal.
3. Body Mass Index (BMI) and Prostate Cancer Risk: Our results suggest that body size, as determined by BMI is inversely associated with PSA and risk of prostate cancer (p =0.0008, 95% CI). We presented these findings at the annual meeting of the American Society of Clnical Oncology (ASCO) in 2008.
4. Carotenoids and Prostate Cancer: We found a protective effect of Lycopene (p =0.02, 95% CI). These findings were presented at the 2006 annual meeting of the American Association for Cancer Research.

5. Quercetin: There was no significant association between risk of prostate cancer or inflammation with intake of quercetin (p =0.63, 95% CI). These findings were presented at the Oregon Dietetic Association’s 2008 annual meeting.